Variant chr20-45095055-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001322799.2(KCNS1):c.1396C>T(p.Arg466Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,613,954 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 14 hom. )

Consequence

KCNS1
NM_001322799.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

KCNS1 (HGNC:6300): (potassium voltage-gated channel modifier subfamily S member 1) Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. [provided by RefSeq, Jul 2008]

KCNS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01020205).

BP6

Variant 20-45095055-G-A is Benign according to our data. Variant chr20-45095055-G-A is described in ClinVar as [Benign]. Clinvar id is 777917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNS1	NM_001322799.2 linkuse as main transcript	c.1396C>T	p.Arg466Cys	missense_variant	4/4	ENST00000537075.3	NP_001309728.1	Q96KK3A2RUL8
KCNS1	NM_002251.5 linkuse as main transcript	c.1396C>T	p.Arg466Cys	missense_variant	5/5		NP_002242.2	Q96KK3A2RUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNS1	ENST00000537075.3 linkuse as main transcript	c.1396C>T	p.Arg466Cys	missense_variant	4/4	1	NM_001322799.2	ENSP00000445595.1		Q96KK3
KCNS1	ENST00000306117.5 linkuse as main transcript	c.1396C>T	p.Arg466Cys	missense_variant	5/5	1		ENSP00000307694.1		Q96KK3

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

341

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00256

AC:

643

AN:

251324

Hom.:

AF XY:

0.00293

AC XY:

398

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00685

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00493

Gnomad FIN exome

AF:

0.000789

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00354

AC:

5176

AN:

1461718

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

2637

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00693

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00489

Gnomad4 FIN exome

AF:

0.000826

Gnomad4 NFE exome

AF:

0.00380

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152236

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00218

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00260

AC:

316

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00279

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

D;D

Eigen

Benign

-0.14

Eigen_PC

Benign

0.0085

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.010

T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.18

B;B

Vest4

0.12

MVP

0.93

ClinPred

0.030

GERP RS

5.6

Varity_R

0.23

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over